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Stomata are pores found in the epidermis of stems or leaves that modulate both plant gas exchange and water/nutrient uptake. The development and function of plant stomata are regulated by a diverse range of environmental cues. However, how carbohydrate status in preexisting leaves might determine systemic stomatal formation within newly developing leaves has remained obscure. The glucose (Glc) sensor HEXOKINASE1 (HXK1) has been reported to decrease the stability of an ethylene/Glc signaling transcriptional regulator, EIN3 (ETHYLENE INSENSITIVE3). EIN3 in turn directly represses the expression of SUC2 (sucrose transporter 2), encoding a master transporter of sucrose (Suc). Further, KIN10, a nuclear regulator involved in energy homeostasis, has been reported to repress the transcription factor SPCH (SPEECHLESS), a master regulator of stomatal development. Here, we demonstrate that the Glc status of preexisting leaves determines systemic stomatal development within newly developing leaves by the HXK1-¦EIN3-¦SUC2 module. Further, increasing Glc levels in preexisting leaves results in a HXK1-dependent decrease of EIN3 and increase of SUC2, triggering the perception, amplification and relay of HXK1-dependent Glc signaling and thereby triggering Suc transport from mature to newly developing leaves. The HXK1-¦EIN3-¦SUC2 molecular module thereby drives systemic Suc transport from preexisting leaves to newly developing leaves. Subsequently, increasing Suc levels within newly developing leaves promotes stomatal formation through the established KIN10ⶠSPCH module. Our findings thus show how a carbohydrate signal in preexisting leaves is sensed, amplified and relayed to determine the extent of systemic stomatal development within newly developing leaves.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Azúcares/metabolismo , Hojas de la Planta/metabolismo , Etilenos/metabolismo , Sacarosa/metabolismo , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismoRESUMEN
Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.
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Ácido Abscísico , Proteínas de Arabidopsis , Arabidopsis , Flores , Regulación de la Expresión Génica de las Plantas , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Arabidopsis/fisiología , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Ácido Abscísico/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Flores/fisiología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Transducción de Señal , Meristema/genética , Meristema/crecimiento & desarrollo , Meristema/metabolismo , Reproducción , Mutación/genética , Quinasas Ciclina-Dependientes/metabolismo , Quinasas Ciclina-Dependientes/genética , Proteínas de HomeodominioRESUMEN
Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.
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Proteínas de Arabidopsis , Arabidopsis , Plantones/metabolismo , Cotiledón/metabolismo , Etiolado , Glucosa/metabolismo , Luz , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fitocromo A/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
BACKGROUND: Type 1 gastric neuroendocrine tumors (NETs) are relatively rare to the extent that some physicians have little experience in diagnosing and treating them. The purpose of this study was to increase the understanding of the disease by analyzing and summarizing the management and prognoses of patients with type 1 gastric NETs at our center. METHODS: The data of 229 patients (59.4% female) with type 1 gastric NETs who were treated at our center during 2011-2022 were retrospectively analyzed. RESULTS: The average patient age was 50.5 ± 10.8 years. Multiple tumors affected 72.5% of the patients; 66.4% of the tumors were < 1 cm, 69.4% were NET G1, and 2.2% were stage III-IV. A total of 76.9% of the patients had received endoscopic management, 60.7% had received traditional Chinese medicine treatment, 10.5% received somatostatin analogues treatment, and 6.6% underwent surgical resection. Seventy patients (41.2%) experienced the first recurrence after a median follow-up of 31 months (range: 2-122 months), and the median recurrence-free time was 43 months. The 1-, 2-, and 3-year cumulative recurrence-free survival rates were 71.8%, 56.8%, and 50.3%, respectively. During a median follow-up of 39 months (range: 2-132 months), one patient had bilateral pulmonary metastasis, and no disease-related deaths were observed. CONCLUSION: Type 1 gastric NETs have a high recurrence rate and a long disease course, underscoring the importance of long-term and comprehensive management.
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Tumores Neuroendocrinos , Neoplasias Gástricas , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/terapia , Tumores Neuroendocrinos/patología , Estudios Retrospectivos , Pronóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapiaRESUMEN
Idarubicin (IDA), an anthracycline antineoplastic drug, is commonly used in the treatment of acute myeloid leukemia (AML) with reasonable response rates and clinical benefits. However, some patients still relapse, or do not respond, and suffer high fatality rates. Recent studies have shown that overexpression of PARP-1 may represent an important risk factor in AML patients. The aim of the present study was to determine the underlying molecular mechanisms by which the PARP-1 inhibitor Olaparib enhances the chemosensitivity of the leukemia cell line K562 and THP1 to IDA. Our data demonstrated that PARP-1 is upregulated in AML patients as well as in K562 and THP1 cells, and that the suppression of PARP-1 activity by Olaparib enhances the inhibitory effect of IDA. A mechanistic study revealed that Olaparib decreases the expressions of p-ATM, p-IκBα, XIAP and p65, and upregulates Bax, cleaved-Caspase-3 and γ-H2AX. Olaparib can enhance the induction of DNA damage by IDA, probably mediated by the inhibition of the ATM-related DNA damage response. Moreover, we also found that the nuclear translocation of p65 and the nuclear export of NEMO are inhibited when IDA and Olaparib are combined. Our results suggest that Olaparib attenuates the activity of the NF-κB pathway and decreases the DNA damage response induced by IDA. Therefore, we conclude that Olaparib is a potentially valuable chemosensitizer for leukemia patients.
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Leucemia Mieloide Aguda , FN-kappa B , Línea Celular Tumoral , Daño del ADN , Humanos , Idarrubicina/farmacología , Idarrubicina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , FN-kappa B/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéuticoRESUMEN
AIM: To investigate paediatric outpatients' nutritional status using bioelectrical impedance analysis and anthropometric z-scores. METHODS: A retrospective data analysis of tertiary paediatric hospital outpatients from 2017 to 2019 was conducted. Patients were categorised into three groups (non-illness, illness and simple obesity) according to clinical diagnoses. The nutritional status was evaluated using anthropometric and bioelectrical impedance analysis. In addition, body composition measurements of patients in three subgroups of the illness group and age- and gender-matched healthy controls were compared. RESULTS: A total of 2015 paediatric outpatients were enrolled. According to body mass index z-scores, undernutrition prevalence among participants was 14.0% (non-illness group, 21.3%; illness group, 11.4%). Body composition measurements indicated that 41.6% of participants had a low fat-free mass index, and the proportions of participants with a low fat-free mass index in the non-illness, illness and simple obesity groups were 48.4, 47.0 and 10.7%, respectively. Compared with healthy controls, the haematology and oncology subgroup had a significantly lower fat-free mass index and fat mass index; the nephrology and rheumatology subgroup had significantly lower height-for-age z-scores but higher fat mass index; and the gastroenterology subgroups had lower fat mass index, fat-free mass index and body mass index z-scores. CONCLUSIONS: The results suggested the low fat-free mass index prevalence was greater than the low body mass index z-score prevalence among paediatric outpatients, and body composition parameters varied across different illnesses. Body composition analysis is recommended in nutrition clinics for accurate paediatric outpatient nutritional assessment, thereby providing timely individualised nutritional interventions.
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Estado Nutricional , Pacientes Ambulatorios , Antropometría , Composición Corporal , Índice de Masa Corporal , Niño , Impedancia Eléctrica , Humanos , Estudios RetrospectivosRESUMEN
Of the multitude of stimuli-responsive microgels, it is still a challenge to achieve multiple responsivenesses to one single stimulus, which can even revert to the corresponding original state autonomously after stimulus. In this work, we reported a series of anthraquinone functionalized microgels (PNI-xVAQ) with thermosensitivity and redox-actuated self-regulating color, size, and fluorescent properties, which were easily synthesized via surfactant-free emulsion copolymerization (SFEP) with N-isopropylacrylamide (NIPAm) as the monomer, 2-vinylanthraquinone (VAQ) as the comonomer, and N,N'-methylenebis(acrylamide) (BIS) as the cross-linker in an aqueous solution at 70 °C. The hydrophobic interactions of comonomer VAQ also led to the formation of internal phase-separated hydrophobic nanodomains in the obtained PNI-xVAQ microgels. The self-regulating color, size, and fluorescence changes of the PNI-xVAQ microgels were reliant on the nonequilibrium redox process of anthraquinone moieties by the addition of sodium dithionite as the chemical fuel to activate the positive feedback that was the reduction of anthraquinone to transient anthraquinone radical anions, following the slow oxidation of anthraquinone radical anions by autonomous "breathing" oxygen in air as the delayed negative feedback. These autonomous self-regulating properties of the PNI-xVAQ microgel were recyclable to a certain extent by repeated feeding of sodium dithionite.
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RATIONALE: Short-chain fatty acids (SCFAs) are associated with intestinal microbiota and diseases in humans. SCFAs have a low response in mass spectrometry, and in order to increase sensitivity, reduce sample consumption, shorten analysis time, and simplify sample preparation steps, a derivatization method was developed. METHODS: We converted seven SCFAs into amide derivatives with 4-aminomethylquinoline. The reaction occurred for 20 min at room temperature. The analytes were separated on a reversed-phase C18 column and quantitated in the positive ion electrospray ionization mode using multiple reaction monitoring. Acetic acid-d4 was used as the stable-isotope-labeled surrogate analyte for acetic acid in the working solutions, while the other stable-isotope-labeled standards were used as internal standards (ISs). RESULTS: Method validation showed that the intra-day and inter-day precision of quantitation for the seven SCFAs over the whole concentration range was ≤3.8% (n = 6). The quantitation accuracy ranged from 85.5% to 104.3% (n = 6). Most important, the collected feces were vortexed immediately with ethanol. CONCLUSIONS: This study provides a new derivatization method for a precise, accurate, and rapid quantitation of SCFAs in human feces using ultra-performance liquid chromatography/tandem mass spectrometry. This method successfully determined the concentration of SCFAs in human feces and could assist in the exploration of intestinal microbiota and diseases.
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Ácidos Grasos Volátiles/análisis , Heces/química , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/economía , Cromatografía Líquida de Alta Presión/métodos , Heces/microbiología , Microbioma Gastrointestinal , Humanos , Espectrometría de Masas en Tándem/economía , Factores de TiempoAsunto(s)
Dolor Abdominal , Fiebre , Dolor Abdominal/etiología , Diagnóstico Diferencial , Femenino , Fiebre/etiología , HumanosRESUMEN
Stratigraphic determination of the Anthropocene, the "Great Acceleration", requires more key globally synchronous stratigraphic markers which reflect the significant human impacts on Earth. Lacustrine sediment magnetic characteristics are of considerable importance in Anthropocene studies because they respond sensitively to environmental changes. There are many shallow lakes in the Songnen Plain (SNP) in northeast China, which are conducive to obtaining Anthropocene sedimentary records. This study explored magnetic materials in lacustrine sediment responses to environmental evolution impact by human activities on the SNP by measuring magnetic parameters in dated sediment cores from 5 shallow lakes in the SNP, northeast China. The results revealed that detrital magnetite and hematite dominated the magnetic minerals in lake sediments. The persistently low value of magnetic susceptibility might be caused by the low content of natural ferrimagnetic minerals in Quaternary fluvial deposits and humus-rich black soil in the catchment, and the loss of magnetic materials during the transport process. In Lake Longjiangpao (LJP), the magnetic concentrations significantly responded to regional precipitation, whereas in the other 4 lakes in the center of the plain, the parameters tended to reflect complex human activities. However, the isothermal remanent magnetization ratio (S-300), which is indicative of the ratio of hematite to magnetite, exhibited relatively consistent variations in the 5 studied lakes. After 1950, the "Great Acceleration", the increase of S-300 indicated a relative proportion of magnetite in sediments, and was positively correlated with the growth of human-activity proxies (Gross Domestic Product (GDP) and population). Thus, this proxy can be regarded as a useful indicator of the beginning of the Anthropocene in the studied region. This study provides new insights into the estimation of local human activities in history and possible evidence for the global definition of the Anthropocene.
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Understanding the historical variations in organic matter (OM) input to lake sediments and the possible mechanisms regulating this phenomenon is important for studying carbon cycling and burial in lake systems; however, this topic remains poorly addressed for macrophyte-dominated lakes. To bridge these gaps, we analyzed bulk OM and molecular geochemical proxies in a dated sediment core from Lake Liangzi, a typical submerged macrophyte-dominated lake in East China, to infer changes in OM input to sediments over the past 169 years due to the intensification of human activities in the catchment. A relatively primitive OM input pattern was observed in ca. 1841-1965, during which the lowest hydrogen index (HI), short-chain n-alkane abundance, and n-C17/n-C16 alkane indicated minimal input from phytoplankton, whereas the high Paq (proxy of aquatic macrophyte input) and long-chain n-alkane abundance suggested dominant and subordinate inputs from submerged and emergent macrophytes, respectively. OM input transitioned during ca. 1965-1993, with the highest Paq and lowest long-chain n-alkane abundance, indicating an increase of submerged macrophyte input and concurrent decline of emergent macrophyte input, probably caused by hydrological regulation practices and land reclamation in the 1960s, respectively. A further shift in OM input was observed since ca. 1993, characterized by the beginning of an increase in phytoplankton input, as indicated by the greater HI, short-chain n-alkane abundance, and n-C17/n-C16 alkane in sediments. Moreover, a lower Paq and higher abundance of long-chain n-alkanes indicated a decline in input from submerged macrophytes and an elevated input from terrestrial plants. The increase in αß-hopane abundance and homohopane index value indicated that petroleum-sourced OM was first introduced into the sediments. The causes of these OM input changes included nutrient influx associated with domestic and industrial discharge, aquaculture within the lake, and widespread deforestation and land clearance in the catchment.
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Monitoreo del Ambiente , Sedimentos Geológicos , Lagos , Lagos/química , China , Sedimentos Geológicos/química , Efectos Antropogénicos , Contaminantes Químicos del Agua/análisisRESUMEN
Anxiety after surgery can be a major factor leading to postoperative cognitive dysfunction, particularly in elderly patients. The role of inhibitory neurons in the basolateral amygdala (BLA) in anxiety-like behaviors in aged mice following isoflurane anesthesia remains unclear. Therefore, the present study aimed to investigate the role of inhibitory neurons in isoflurane-treated mice. A total of 30 C57BL/6 mice (age, 13 months) were allocated into the control and isoflurane anesthesia groups (15 mice/group) and were then subjected to several neurological assessments. Behavioral testing using an elevated plus maze test showed that aged mice in the isoflurane anesthesia group displayed significant anxiety-like behavior, since they spent more time in the closed arm, exhibited more wall climbing behavior and covered more distance. In addition, whole-cell patch-clamp recording revealed that the excitability of the BLA excitatory neurons was notably increased following mice anesthesia with isoflurane, while that of inhibitory neurons was markedly reduced. Following mice treatment with diazepam, the excitability of the BLA inhibitory neurons was notably increased compared with that of the excitatory neurons, which was significantly attenuated. Overall, the results of the current study indicated that anxiety-like behavior could occur in aged mice after isoflurane anesthesia, which could be caused by a reduced excitability of the inhibitory neurons in the BLA area. This process could enhance excitatory neuronal activity in aged mice, thus ultimately promoting the onset of anxiety-like behaviors.
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This paper studies how to flexibly integrate reconstructed 3D models into practical 3D modeling pipelines such as 3D scene creation and rendering. Due to the technical difficulty, one can only obtain rough 3D models (R3DMs) for most real objects using existing 3D reconstruction techniques. As a result, physically-based rendering (PBR) would render low-quality images or videos for scenes that are constructed by R3DMs. One promising solution would be representing real-world objects as Neural Fields such as NeRFs, which are able to generate photo-realistic renderings of an object under desired viewpoints. However, a drawback is that the synthesized views through Neural Fields Rendering (NFR) cannot reflect the simulated lighting details on R3DMs in PBR pipelines, especially when object interactions in the 3D scene creation cause local shadows. To solve this dilemma, we propose a lighting transfer network (LighTNet) to bridge NFR and PBR, such that they can benefit from each other. LighTNet reasons about a simplified image composition model, remedies the uneven surface issue caused by R3DMs, and is empowered by several perceptual-motivated constraints and a new Lab angle loss which enhances the contrast between lighting strength and colors. Comparisons demonstrate that LighTNet is superior in synthesizing impressive lighting, and is promising in pushing NFR further in practical 3D modeling workflows.
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BACKGROUND: Gastric cancer (GC) is the fifth most common and the fourth most lethal malignant tumour in the world. Most patients are already in the advanced stage when they are diagnosed, which also leads to poor overall survival. The effect of postoperative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local recurrence. AIM: To investigate the safety and efficacy of a programmed cell death 1 (PD-1) inhibitor combined with oxaliplatin and S-1 (SOX) in the treatment of Borrmann large type III and IV GCs. METHODS: A retrospective analysis (IRB-2022-371) was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy (NAT) from January 2020 to December 2021. According to the different neoadjuvant treatment regimens, the patients were divided into the SOX group (61 patients) and the PD-1 + SOX (P-SOX) group (28 patients). RESULTS: The pathological response (tumor regression grade 0/1) in the P-SOX group was significantly higher than that in the SOX group (42.86% vs 18.03%, P = 0.013). The incidence of ypN0 in the P-SOX group was higher than that in the SOX group (39.29% vs 19.67%, P = 0.05). The use of PD-1 inhibitors was an independent factor affecting tumor regression grade. Meanwhile, the use of PD-1 did not increase postoperative complications or the adverse effects of NAT. CONCLUSION: A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.
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OBJECTIVE: To elucidate the safety and effectiveness of laryngeal mask airway (LMA) use in pediatric patients undergoing laparoscopic inguinal hernia repair. METHODS: Studies were searched on the PubMed, EMBASE, and Cochrane Library databases. Only randomized controlled trials (RCTs) were included. Primary outcomes were major perioperative respiratory adverse events (PRAEs), namely laryngospasm, bronchospasm, desaturation, and aspiration. Secondary outcomes were minor PRAEs, anesthesia time, and recovery time. A meta-analysis was performed to calculate risk ratios (RR), weighted mean difference (WMD), and 95 % confidence intervals (CI) by using random effects models. RESULTS: In total, 5 RCTs comprising 402 patients were included. Regarding major PRAEs, laryngospasm (RR: 0.43, 95 % CI: 0.12 to 1.47; p = 0.18), bronchospasm, and aspiration all demonstrated no difference between the laryngeal and endotracheal groups. Desaturation exhibited a trend, but this trend was not sufficiently supported with statistical evidence (p = 0.09). For minor PRAEs, fewer patients experienced incidence of cough after laryngeal mask use (RR: 0.27, 95 % CI: 0.11 to 0.67; p = 0.005). Other PRAE, namely hoarseness (p = 0.06), sore throat (RR: 1.88, 95 % CI: 0.76 to 4.66; p = 0.18), and stridor, did not differ between the 2 groups. Additionally, both anesthesia time (WMD: -6.88 min, 95 % CI: -11.88 to -1.89; p < 0.00001) and recovery time (WMD: -4.85 min, 95 % CI: -6.51 to -3.19; p < 0.00001) were shortened in the LMA group. CONCLUSION: LMA used in pediatric laparoscopic inguinal hernia repair demonstrated no greater safety risks than endotracheal tube intubation did. Thus, anesthesiologists may shift from conventional endotracheal tube use to LMA use. Moreover, anesthesia and recovery times were shortened in the LMA group, which resulted in more efficient use of the operating room. Because of these benefits, LMA could be an appropriate option for pediatric patients undergoing laparoscopic inguinal hernia repair. LEVEL OF EVIDENCE: Treatment Study, LEVEL III.
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Hernia Inguinal , Herniorrafia , Laparoscopía , Máscaras Laríngeas , Humanos , Máscaras Laríngeas/efectos adversos , Hernia Inguinal/cirugía , Laparoscopía/métodos , Laparoscopía/efectos adversos , Niño , Herniorrafia/métodos , Herniorrafia/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
Hematological indicators of chronic systemic inflammation are significant biomarkers for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). We performed a systematic review and meta-analysis to assess the impact of certain factors on the overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of patients with GEP-NENs. These factors include the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and C-reactive protein (CRP) levels. After searching the Medline, Embase, and Cochrane Library databases from January 1, 2000 to October 20, 2022 and the American Society of Clinical Oncology conference proceedings from January 1, 2017, hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted. Subgroup analyses were conducted to identify the origins of heterogeneity and examine the impact of factor grouping. The effects of the cut-off values and sample size were assessed by meta-regression. The results revealed that higher NLRs, PLRs, and CRP levels were associated with shorter OS (HR = 2.09, 95% CI = 1.55-2.8; HR = 1.79, 95% CI = 1.40-2.28; and HR = 2.88, 95% CI = 2.09-3.95, respectively; all p < 0.001). Higher NLRs and lower LMRs were associated with shorter DFS (HR = 3.34, 95% CI = 2.11-5.29 and HR = 2.71, 95% CI = 2.27-3.24, respectively; both p < 0.001). Higher PLRs and CRP levels were correlated with shorter PFS (HR = 3.48, 95% CI = 1.34-9.03, p = 0.01 and HR = 3.14, 95% CI = 1.63-6.08, p = 0.001). As demonstrated in the research, hematological indicators of systemic inflammation are promising biomarkers for GEP-NEN assessment.
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Linfocitos , Tumores Neuroendocrinos , Humanos , Pronóstico , Biomarcadores/metabolismo , Linfocitos/metabolismo , Inflamación/metabolismo , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/metabolismoRESUMEN
In this research, we explored their capacity for Narcissoside antioxidant and anticholinergic, antidiabetic, and anti-acute myeloid leukaemia. Narcissoside's antioxidant activities were elucidated by the use of various bioanalytical assays. Narcissoside's radical scavenging activities were evaluated by DPPH⢠and ABTSâ¢+ scavenging activities. On the other hand, IC50 values were calculated for DPPHâ¢, and ABTSâ¢+ scavenging, acetylcholinesterase, and α-glucosidase inhibition effects of narcissoside. IC50 values narcissoside, as 11.54 nM for AChE and 65.58 nM for α-glucosidase were calculated with % Activity-[Inhibitory] graphs. Then, ADME/T analysis of narcissoside molecule was performed to calculate the drug becoming parameters.
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Enfermedad de Alzheimer , Leucemia Mieloide , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Inhibidores de la Colinesterasa/farmacología , Simulación del Acoplamiento Molecular , alfa-Glucosidasas , Acetilcolinesterasa , Enfermedad de Alzheimer/tratamiento farmacológicoRESUMEN
The abundance and composition of aliphatic hydrocarbon biomarkers were determined in dated sediment cores from Lakes Qijiapao (QJP) and Huoshaoheipao (HSH) in the Songnen Plain, Northeast China, to investigate historical environmental changes in these lakes and identify likely controlling factors. Based on these results, the recent environmental history of the two lakes can be divided into three periods. Before 1950, low Paq values (avg. 0.23 and 0.27, respectively) and middle-chain n-alkane abundances (normalized to total organic carbon, avg. 14.82 and 16.01 µg g-1 TOC, respectively) in both lakes suggested low aquatic productivity and the limited input of submerged macrophyte organic matter (OM). However, the significant increase in the abundance of short-chain n-alkanes in Lake HSH (from 8.34 to 16.68 µg g-1 TOC) indicated the emergence of early nutrient enrichment in the lake. From 1950 to 2000, marked increase in the abundance of middle-chain n-alkanes (avg. 21.72 and 22.62 µg g-1 TOC in Lakes QJP and HSH, respectively) and Paq values indicated that both lakes had undergone eutrophication because of the population explosion and agricultural intensification. From 2000 to 2013, the abundance of short- and middle-chain n-alkanes in Lake QJP markedly exceeded those in Lake HSH and indicated a larger eutrophication in Lake QJP, which could be caused by the development of ecotourism in Lake HSH and the concomitant increase in aquaculture in Lake QJP in recent years. The highest abundance of C30 αß-hopane (~ 10.24 µg g-1 TOC) and the lowest CPIH values in Lake QJP revealed a possible petroleum pollution since 2008. Taken together, lake eutrophication in the Songnen Plain accelerated after 1950 and was influenced primarily by agriculture and aquaculture. This is in contrast to lakes in other regions of China (such as the Yangtze River Basin and Yunnan Province), where urbanization and industrialization have exerted a dominant influence on the lake environment.
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Sedimentos Geológicos , Hidrocarburos , Humanos , China , Sedimentos Geológicos/química , Hidrocarburos/análisis , Alcanos/análisis , Eutrofización , Monitoreo del Ambiente/métodosRESUMEN
Introduction: Mantle cell lymphoma (MCL) can be stratified into blastoid and classical subtypes based on morphological features, with the former subtype having a poorer prognosis. Despite recent advances in targeted approaches, including multiple bruton tyrosine kinase inhibitors which yield impressive clinical responses and improve prognoses, MCL remains an incurable disease with frequent relapses. Additional therapeutic interventions are therefore unmet medical needs for the management of patients with MCL. Methods: Cell viability and apoptosis assays were employed to analyze the therapeutic interaction of venetoclax combined with selinexor in MCL cells. Western blot was used to investigate the potential mechanism of action for the synergy of venetoclax in combination with selinexor in MCL cells. Results: In this study, we revealed that both blastoid and classical MCL cells were vulnerable to the cytotoxic effects of selinexor, a well-established XPO1 inhibitor, manifested by loss of cell viability and induction of cell apoptosis. Moreover, our data indicated that the addition of venetoclax to selinexor showed synergistically decreased cell viabilities and increased cell deaths in blastoid and classical MCL cells compared to each single drug treatment. Either selinexor or venetoclax treatment alone decreased MCL1 expressions and increased BAX levels in MCL cells, and these effects were further enhanced by their combined regimen. Mechanistically, our findings demonstrated that induction of DNA damage and inactivation of DNA damage response were involved in the synergistic interaction of the drug combination regimen. Conclusion: Collectively, this study might provide a potential attractive therapy option for the treatment of MCL. However, the conclusion needs additional experimental validation in in vivo models and clinical evaluations are mandatory.
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Linfoma de Células del Manto , Humanos , Adulto , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/patología , Recurrencia Local de Neoplasia , Daño del ADN , Línea Celular TumoralRESUMEN
Limited human activities in catchments make remote alpine lakes valuable sites for studying the evolution of lake environments in response to climate change and atmospheric deposition; however, this issue remains rarely studied owing to the scarcity of monitoring data. In this study, water quality evolution in Lake Jiren, a remote alpine lake on the southeastern margin of the Tibetan Plateau, over the past two centuries was reconstructed through geochemical analyses of aliphatic hydrocarbons, major and trace elements, and organic matter (OM) pyrolysis products in a dated sediment core, and the associated drivers were identified by temporally comparing the geochemical results with document records. All geochemical data demonstrated that the lake water remained relatively pure until 1947, after which the n-alkane and αß-hopane proxies indicated eutrophication and petroleum contamination. The OM pyrolysis proxy hydrocarbon index indicated more eutrophic conditions after 1957. Concurrently, hypolimnetic deoxygenation increased, as indicated by redox-sensitive proxies, such as the enrichment factors (EFs) of molybdenum (Mo). These proxies recorded further intensification of deoxygenation after 1976. The EFs for other trace elements indicated cadmium contamination after 1967. The greater anthropogenic emissions of reactive nitrogen, petroleum products, and heavy metals in East and South Asia since approximately 1950 and the subsequent atmospheric transport of these materials to the lake might be the basic driver of water quality deterioration. Eutrophication induced by nitrogen deposition was responsible for increased hypolimnetic deoxygenation by enhancing phytoplankton productivity and OM input. The further intensification of deoxygenation was attributed to climate warming since the 1970s, as prolonged water column stratification under this condition decreased oxygen input from the epilimnion to the lake bottom. These findings may be beneficial for understanding the natural and anthropogenic effects on the water quality of alpine lakes and help in the environmental management of Lake Jiren and other alpine lakes.